Abstract | OBJECTIVE: DESIGN AND METHODS: Mutational analysis of NR5A1 in 60 individuals with varying degrees of hypospadias from the German DSD network. RESULTS: Heterozygous NR5A1 mutations were found in three out of 60 cases. These three individuals represented the most severe end of the spectrum studied as they presented with penoscrotal hypospadias, variable androgenization of the phallus and undescended testes (three out of 20 cases (15%) with this phenotype). Testosterone was low in all three patients and inhibin B/anti-Müllerian hormone (AMH) were low in two patients. Two patients had a clear male gender assignment. Gender re-assignment to male occurred in the third case. Two patients harbored heterozygous nonsense mutations (p.Q107X/WT, p.E11X/WT). One patient had a heterozygous splice site mutation in intron 2 (c.103-3A/WT) predicted to disrupt the main DNA-binding motif. Functional studies of the nonsense mutants showed impaired transcriptional activation of an SF-1-responsive promoter (Cyp11a). To date, adrenal insufficiency has not occurred in any of the patients. CONCLUSIONS:
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Authors | Birgit Köhler, Lin Lin, Inas Mazen, Cigdem Cetindag, Heike Biebermann, Ilker Akkurt, Rainer Rossi, Olaf Hiort, Annette Grüters, John C Achermann |
Journal | European journal of endocrinology
(Eur J Endocrinol)
Vol. 161
Issue 2
Pg. 237-42
(Aug 2009)
ISSN: 1479-683X [Electronic] England |
PMID | 19439508
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Hydroxyprogesterones
- NR5A1 protein, human
- Steroidogenic Factor 1
- inhibin B
- Testosterone
- Inhibins
- Dehydroepiandrosterone Sulfate
- Anti-Mullerian Hormone
- Follicle Stimulating Hormone
- DNA
- Hydrocortisone
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Topics |
- Adrenal Insufficiency
(blood, genetics)
- Anti-Mullerian Hormone
(blood)
- Cohort Studies
- DNA
(chemistry, genetics)
- Dehydroepiandrosterone Sulfate
(blood)
- Follicle Stimulating Hormone
(blood)
- Humans
- Hydrocortisone
(blood)
- Hydroxyprogesterones
(blood)
- Hypospadias
(blood, genetics)
- Infant, Newborn
- Inhibins
(blood)
- Male
- Mutagenesis, Site-Directed
- Mutation
- Sequence Analysis, DNA
- Steroidogenic Factor 1
(genetics)
- Testosterone
(blood)
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